This program concerns the physiologic effects, adaptive changes and functional deterioration induced by acute and chronic exposure to altered respiratory gas composition, pressure and temperature at rest and in exercise. The respiratory conditions of special interest are hyperoxygenation (to the limits of tolerance); hypoxic and sub-atmospheric pressure; substitution of helium, neon, argon or mixtures for atmospheric nitrogen; increase in ambient pressure and respiratory gas density and exposure to abnormalities of temperature control at increased ambient pressure. Under conditions of natural extremes, or in contrived alterations of environmental pressure and gas characteristics, respiratory gases can sustain life or can induce dysfunction, permanent damage or death. For oxygen, only a narrow range of partial pressures is tolerated by living cells between the metabolic failure of hypoxia and the metabolic poisoning by hyperoxia. Deviations from normal internal carbon dioxide pressure lead to permanent adjustments in acid-base and respiratory control functions. Elevation of some inert "carrier" gases induces narcosis and possible adaptation to it. Respiratory control is modified by increased oxygen pressure and increased gas density. Excessive rates of change of inert gas pressure in body tissue relative to ambient pressure leads to development of gas lesions or lethal gas embolization. Physical stresses, change in hydrostatic pressure itself, and temperature alteration itself can produce incapacitating effects, magnified by influences of respiratory gases. This program undertakes the quantitative definition of these effects produced by individual respiratory gases, and relates these individual effects to the composite influence of whole body exposure to specific respiratory environments of undersea activity, altitude exposure, hyperoxygenation therapy and anesthesia.